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Background Immune checkpoint inhibitors (ICIs) improve the outcomes across solid tumours, although they can cause severe immune-related adverse events (irAEs). Due to this possibility of side effects, practical and low-cost predictors of severe irAEs are needed to guide patient monitoring and care. Methods We conducted a single-centre retrospective cohort study involving 593 patients who were treated with anti-PD-1/PD-L1 monotherapy or anti-PD-1/PD-L1 plus anti-CTLA-4 combination therapy from June 2016 to November 2024. The primary endpoint was the time to the first severe irAE (grade ≥ 3). Peripheral blood biomarkers were evaluated at baseline and immediately before the cycle 3. The cumulative incidence was estimated, and the associations were quantified using the Fine–Gray subdistribution hazards ratio (sHR) model in a competing risks framework. Results Overall, 11.6% of patients experienced a severe irAE, with the median time to the first event being 12 weeks and the most frequent severe irAE being colitis ( n  = 21; 3.5%). Combination therapy was associated with a higher risk when compared with monotherapy (sHR 3.71, 95% confidence interval [CI] 2.25–6.13). Baseline eosinophils > 250/µL were associated with an increased risk (sHR 2.22, 95% CI 1.35–3.65). A lower red cell distribution width (RDW) was likewise associated with the risk at two timepoints: baseline RDW ≤ 15.8% (sHR 2.60, 95% CI 1.35–5.01) and pre-cycle 3 RDW ≤ 14.3% (sHR 2.71, 95% CI 1.44–5.09). The effects were directionally consistent across subgroups, and no interactions were detected. The other blood biomarkers tested were not significant (all p  > 0.05). Conclusions A high baseline eosinophil count and a lower RDW early on during therapy identify patients at increased risk of severe irAEs. These accessible measures could support personalised monitoring and biomarker-guided patient selection. However, external validation is needed to confirm the robustness and validate the thresholds identified in this study prior to clinical use.

To mitigate this risk, systemic adjuvant therapy is required.1 Adjuvant administration of a combination of dabrafenib and trametinib yielded a significantly reduced risk of recurrence and enhanced survival outcome in patients diagnosed with stage III melanoma and carrying the BRAF V600E or V600K mutation (hazard ratio 0.51).2 With the increased use of these agents for melanoma and other indications, clinicians should be aware of rare but potentially life-threatening side effects associated with these medications. Authorship Contributions: Design- A.G., B.K., Supervision- B.K., Data Collection and Processing- Y.Ç., O.Ö., F.P.A., Writing- A.G., S.Ö. Conflict of Interest: No conflict of interest was declared by the authors. PLoS One. 2012;7:e29506. Aslı Geçgel1, Sercan Ön2, Yeliz Çiftçi3, Oğuzcan Özkan1, Fatma Pınar Açar1, Burçak Karaca1 1Clinic of Medical Oncology, Ege University Hospital, İzmir, Türkiye; 2Clinic of Medical Oncology, İzmir Bayraklı City Hospital, İzmir, Türkiye; 3Clinic of Neurology, Bakırçay University Çiğli Training and Research Hospital, İzmir, Türkiye

Immune checkpoint inhibitors (ICIs) have significantly improved the five-year survival rate for advanced melanoma. However, many patients exhibit resistance to ICI therapy. This study evaluated the efficacy and prognostic factors of anti-PD-1 (Group A) and nivolumab–ipilimumab (Group B) therapy in patients with advanced melanoma who were resistant to prior ICI therapy. We conducted a retrospective analysis of 56 patients with advanced melanoma who had previously shown resistance to ICI therapy. In the Group A (who have previously shown resistance to anti-CTLA-4, n = 28), the objective response rate (ORR) was 42.9%, with a disease control rate (DCR) of 53%. In the Group B (previously shown resistance to anti-PD-1, n = 28), the ORR was 17.9%, and the DCR was 25%. The ORR was lower in two subgroups: patients who showed progression or relapse in the the initial radiological assessment of prior ICI therapy (ORR 10.5%) and patients who had previously received ICI in the adjuvant setting (ORR 8.3%). A Royal Marsden Hospital (RMH) score of 2–3 was a predictor of OS in both groups (Group A: HR 3.789, 95% CI 1.356–10.589, p = 0.011; Group B: HR 4.281, 95% CI 1.490–12.300, p = 0.007) and for PFS in the Group B (HR 3.167, 95% CI 1.062–9.442, p = 0.039). Anti-PD-1 therapy demonstrated efficacy following resistance to anti-CTLA-4, whereas combination ICI therapy showed lower response rates in patients resistant to anti-PD-1. Further studies are needed to confirm the RMH scores and other prognostic markers and to evaluate subgroups with lower efficacy of nivolumab-ipilimumab therapy.

Background/Objectives: Nivolumab has been shown to be an effective treatment for metastatic renal cell carcinoma (mRCC); however, patient responses vary considerably. The objective of this study is to evaluate the prognostic value of the C-PLAN index in predicting survival outcomes for patients with mRCC treated with nivolumab. Methods: This retrospective cohort study included 81 mRCC patients previously treated with tyrosine kinase inhibitors who subsequently received nivolumab. The C-PLAN index, which includes C-reactive protein, performance status, lactate dehydrogenase, albumin, and derived neutrophil-to-lymphocyte ratio, was used to classify patients into “good” and “poor” prognostic groups. Results: The median overall survival (OS) was 22 months, and the median progression-free survival (PFS) was 6.7 months. Patients in the “poor” C-PLAN group exhibited significantly shorter OS and PFS than those in the “good” group (median OS: 13 vs. 31 months, p = 0.003; median PFS: 3 vs. 10 months, p = 0.007). The C-PLAN index was identified as an independent predictor of both OS (HR = 1.19, 95% CI: 1.11–3.43, p = 0.020) and PFS (HR = 1.71, 95% CI: 1.04–2.78, p = 0.032) in multivariate analysis. Conclusions: These findings suggest that the C-PLAN index may serve as a valuable prognostic tool, offering insights into survival outcomes for patients undergoing nivolumab therapy. Further prospective and multicenter studies are warranted to validate its clinical utility.

Kamu borçlanmasını etkileyen faktörler dikkate alındığında bunlar, kamu borç oranı ve borç dinamikleridir. Bu çalışma, Türkiye ekonomisinde borç dinamiklerini belirleyen temel makroekonomik değişkenleri incelemeyi amaçlamaktadır. 2009Q1–2024Q4 dönemi çeyreklik verileri kullanılarak ARDL eşbütünleşme yaklaşımı ve hata düzeltme modeli (ECM) çerçevesinde, borç stoku/GSYH oranının uzun dönemli belirleyicileri olarak enflasyon, faiz dışı denge, faiz oranı – büyüme farkı (r–g), kriz dönemleri ve borç stokundaki değişim analiz edilmektedir. Sonuç olarak, uzun dönemde borç stokunun enflasyon, faiz dışı denge, faiz oranı – büyüme farkı, kriz dönemleri ve borç artışı gibi değişkenlerden etkilendiği tespit edilmiştir. Özellikle r-g farkı ve kriz dönemleri borç yükünü artırıcı en güçlü faktörler olarak öne çıkarken; enflasyon ve faiz dışı denge borç stokunu azaltıcı yönde katkı sağlamaktadır. Borcun sürdürülebilirliği için faiz oranın büyüme oranından yüksek olduğu koşulda hükümetlerin yeteri düzeyde faiz dışı fazla verilmesi gerektiğine dikkat çekilmiştir. Bu sonuçlar, borç dinamiği açısından faiz–büyüme farkının kontrol altında tutulması gerekliliğini ve faiz dışı dengenin kritik rolünü teyit etmektedir.

Immune checkpoint inhibitors (ICIs) have transformed the therapeutic landscape of malignant melanoma; however, they are frequently associated with immune-related adverse events (irAEs). Emerging evidence suggests that genetic predispositions, including interleukin-7 (IL-7) gene variants, may influence the risk of these toxicities. In this single-center retrospective study, we investigated the potential utility of IL-7 rs16906115 polymorphism and lymphocyte stability index (LSI) in predicting susceptibility to irAEs among 96 melanoma patients treated with ICIs. Genotyping revealed a minor allele frequency of 8.3% for rs16906115. Logistic regression analysis indicated that carriers of the minor allele had a significantly increased risk of all-grade irAEs compared to reference allele carriers (adjusted OR: 3.93; 95%CI:1.13-13.64; p=0.031). Subgroup analyses revealed a significant increase in risk across endocrine, non-cutaneous, multiple, low-grade, and early onset (<3 months) irAEs. While neither baseline lymphocyte count nor LSI predicted overall irAE incidence, an elevated LSI emerged as a key risk factor for early steroid-requiring irAEs (adjusted OR:3.79; 95% CI: 1.14-12.61; p =0.030). These findings from a Turkish cohort corroborate earlier European studies suggesting that rs16906115 minor allele carriage may be a genetic risk factor for irAEs. Furthermore, LSI may serve as a dynamic biomarker for predicting early steroid-requiring irAEs. Prospective multicenter studies among diverse populations are warranted to validate these findings.

Background: Although immune checkpoint inhibitors (ICIs) have significantly improved cancer treatment, a substantial proportion of patients do not benefit from these therapies, revealing the crucial need to identify reliable biomarkers. Inflammatory markers, such as the neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), pan-immune inflammation value (PIV), systemic inflammation response index (SIRI), lactate dehydrogenase (LDH), and C-reactive protein (CRP), may provide insights into treatment outcomes. Objectives: This study aimed to evaluate the prognostic value of multiple inflammatory markers in patients with cancer receiving ICI-based therapies. Methods: A retrospective analysis was performed on 226 patients treated with ICI-based therapies at a single center between 2012 and 2023. The inflammatory markers NLR, PIV, SII, SIRI, LDH, CRP, and albumin were assessed. Cut-off values were determined using maximally selected rank statistics, and overall survival (OS) and progression-free survival (PFS) were evaluated using the Kaplan–Meier method and Cox regression analysis. Results: High NLR, PIV, SII, SIRI, LDH, and CRP, as well as low albumin levels, were associated with worse OS and PFS (p < 0.001). In the multivariate analysis, high CRP, LDH, NLR, PIV, and SII independently predicted worse OS. Conclusions: Our findings confirm the prognostic utility of several inflammatory biomarkers in patients with cancer receiving ICIs, highlighting their potential for treatment stratification. Further studies are necessary to standardize cut-off values and validate these findings across broader, more diverse populations.

Objectives:The present study aims to determine the frequency of cyber victimization, variables associated with the pandemic, and families’ attitudes toward children’s internet use, and to understand the coping methods of adolescents during the coronavirus disease-2019 pandemic.Materials and Methods:One hundred forty-two patients between the ages of 12 and 18, who applied face-to-face or online Child Psychiatry Department of Kocaeli University during the pandemic period, were included in the study. The Sociodemographic Data Form was administered to parents, the Cyberbullying Scale for Adolescents, the Coping with Cyberbullying Scale for Adolescents, and the Internet Family Attitude Scale to adolescents.Results:It was found that 69% of adolescents were exposed to cyberbullying at least once during the pandemic, 59.2% were female, and the mean age was 14.64±1.81. Adolescents are mostly cyberbullied while playing games (21.8%), text messaging (21.8%), and using social networks (9.9%). Victims most frequently used online security as a coping method and sought significantly less help. It was determined that in families, a negligent attitude is associated with being a cyber victim, despite the high rates.Conclusion:It was determined that cyber victimization in adolescents was high during the pandemic, families were not aware of this situation, and young people did not use appropriate coping methods. In the literature, there are a limited number of studies on adolescents regarding cyber victimization during the pandemic. It is thought that our study is essential to take precautions and make appropriate referrals in a long-lasting pandemic.

Bilindiği gibi regresyon analizi değişkenler arasındaki sebep-sonuç ilişkisini ortaya koymak amacı ile yapılmaktadır. Regresyon analizinde parametrelerin tahmin edilmesi amacıyla en çok kullanılan ve en bilinen teknik olağan en küçük kareler tekniğidir. Ancak bu tekniğin kullanımı birçok varsayımı gerekli kılmaktadır[ 1 ]. Bu varsayımların en önemlilerinden biri, hata terimlerinin normal dağılıma sahip olmasıdır. Ancak söz konusu varsayımın gerçekleşmesi için öncelikle hem bağımlı hem de bağımsız değişkenlerin sürekli olmaları gerekmektedir. Uygulamada ise zaman zaman bağımlı, zaman zaman da bağımsız değişkenlerin nitel yapıda oldukları görülmektedir.

With the development of technology, new techniques have started to be used in education. According to the literature, the use of technology in education makes learning more permanent. Concrete steps have also been taken in our country for this purpose. FATIH and EBA projects are among the projects implemented for this purpose recently. With these projects, tablets were distributed to schools and smart boards were installed. As a result of the projects, the use of technology has increased, but the expected result has not been achieved. (Dursun vd., 2015) Nevertheless, the use of technology has been recommended and encouraged both by the Ministry of National Education and in academic studies. Before Covid19, the use of technology in education was left to the preference of students and teachers, but during the pandemic, it has become mandatory.The aim of this research is to determine the attitudes of geography teachers towards distance education in Buca high schools. The source of the study is to find out whether there is a direct or indirect relationship between online education and teachers' attitudes. The relevance of the study and its impact on the whole world has made it an interesting topic. The population of the study consists of geography teachers working in Buca district. The attitudes of geography teachers towards online education were obtained by using the \"Attitude Scale for Distance Education\" prepared by Agir et al. (2007) with the necessary permissions. T-test, frequency, percentage analysis (ANOVA) were performed for the analysis of the problem and sub-problems of the collected data.When literature review was conducted, many studies related to online education were found in the YOK thesis. Being the first research conducted in this field in YOK thesis reveals its original value. The study gains importance as it will contribute to the literature in the geography field and to the subsequent studies regarding the attitudes of educators towards distance education due to the Covid-19 pandemic.